Trastuzumab Deruxtecan in HER2-Positive Metastatic Breast Cancer Patients with Brain Metastases: A DESTINY-Breast01 Subgroup Analysis.

Unlabelled: DESTINY-Breast01 (NCT03248492) evaluated trastuzumab deruxtecan (T-DXd; DS-8201) in patients with heavily pretreated HER2-positive metastatic breast cancer (mBC). We present a subgroup of 24 patients with a history of treated brain metastases (BM), a population with limited treatment options. In patients with BMs, the confirmed objective response rate (cORR) was 58.

Trastuzumab Deruxtecan versus Trastuzumab Emtansine for Breast Cancer.

Background: Trastuzumab emtansine is the current standard treatment for patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer whose disease progresses after treatment with a combination of anti-HER2 antibodies and a taxane.

Methods: We conducted a phase 3, multicenter, open-label, randomized trial to compare the efficacy and safety of trastuzumab deruxtecan (a HER2 antibody-drug conjugate) with those of trastuzumab emtansine in patients with HER2-positive metastatic breast cancer previously treated with trastuzumab and a taxane. The primary end point was progression-free survival (as determined by blinded independent central review); secondary end points included overall survival, objective response, and safety.

Design, characterization, and intracellular trafficking of biofunctionalized chitosan nanomicelles.

The hydrophobically modified glycol chitosan (HGC) nanomicelle has received increasing attention as a promising platform for the delivery of chemotherapeutic drugs. To improve the tumor selectivity of HGC, here an avidin and biotin functionalization strategy was applied. The hydrodynamic diameter of the biotin-avidin-functionalized HGC (cy5.

Interleukin-6 increases matrix metalloproteinase-14 (MMP-14) levels via down-regulation of p53 to drive cancer progression.

Matrix metalloproteinases (MMPs) play critical roles in cancer invasion and metastasis by digesting basement membrane and extracellular matrix (ECM). Much attention has focused on the enzymatic activities of MMPs; however, the regulatory mechanism of MMP expression remains elusive. By employing bioinformatics analysis, we identified a potential p53 response element within the MMP-14 promoter.

Assessment of Matrix Metalloproteinases by Gelatin Zymography.

Matrix metalloproteinases are endopeptidases responsible for remodeling of the extracellular matrix and have been identified as critical contributors to breast cancer progression. Gelatin zymography is a valuable tool which allows the analysis of MMP expression. In this approach, enzymes are resolved electrophoretically on a sodium dodecyl sulfate-polyacrylamide gel copolymerized with the substrate for the MMP of interest.

Targeting Matrix Metalloproteinases in Cancer: Bringing New Life to Old Ideas.

Since the identification of matrix metalloproteinases (MMPs), a family of zinc-dependent endopeptidases, as being a driving factor for cancer progression and patient prognosis, MMPs have been studied extensively. Although early programs targeting MMPs were largely unsuccessful in clinical trials, they remain a viable and highly desirable therapeutic target based on preclinical studies and their role in disease progression. As information regarding the structure and function of these proteinases is compiled and biotechnology evolves, tools to develop better inhibitors is within our grasp.

Hypoxia promotes colon cancer dissemination through up-regulation of cell migration-inducing protein (CEMIP).

Hypoxic stress drives cancer progression by causing a transcriptional reprogramming. Recently, KIAA1199 was discovered to be a cell-migration inducing protein (renamed CEMIP) that is upregulated in human cancers. However, the mechanism of induction of CEMIP in cancer was hitherto unknown.

MMP Inhibitors: Past, present and future.

Development of inhibitors of matrix metalloproteinases (MMPs) has been fraught with challenges. Early compounds largely failed due to poor selectivity and bioavailability. Dose-limiting side effects, off-target interactions, and improperly designed clinical trials significantly impeded clinical success.